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Background: Colonic motility is regulated by various factors along the gut‐brain axis; however, detailed mechanisms are unknown. This study aimed to examine the involvement of the autonomic nervous system in colonic motility. Suncus murinus (suncus) is a small laboratory mammal suitable for gastrointestinal motility studies. Methods: Colonic motility and concomitant feeding and defecation behaviors in vagotomized and reserpine‐administered suncus were recorded simultaneously for 24 h. Furthermore, we performed immunohistochemistry on tyrosine hydroxylase (TH) and in situ hybridization on corticotropin‐releasing hormone (CRH) in suncus brain. Additionally, we examined c‐Fos expression in the brain using immunohistochemistry in conscious suncus with colorectal distension. Key Results: In vagotomized suncus, clustered giant migrating contractions (GMCs), consisting of strong contractions occurring in a short time, were observed, and the percentage of GMCs without defecation increased. The frequency of GMCs in the reserpine‐administered suncus increased during a light period (ZT0‐4, 4–8) and decreased during a dark period (ZT16‐20, 20–24) compared to a vehicle group. Additionally, the percentage of GMCs without defecation in the reserpine‐administered suncus increased. Suncus TH‐immunopositive neurons were found in the locus coeruleus (LC), as shown in rodents. In contrast, CRH mRNA‐expressing cells were not observed in a region assumed to be the Barrington's nucleus (Bar). Furthermore, colorectal distension in conscious suncus induced c‐Fos expression in LC TH neurons. Conclusions & Inferences: Our results suggest that the vagus and sympathetic nerves are not required for induction of GMCs in vivo. However, they are likely to exert a modulatory role in control of GMC frequency in Suncus murinus. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the fundamental mechanisms of colonic motility in the house musk suncus (Suncus murinus) as an established animal model of gut motility. Methods: To measure gut motility in free‐moving conscious suncus, strain gauge force transducers were implanted on the serosa of the colon and gastric body. Key Results: We recorded diurnal changes in colonic motility and observed the relationship between feeding and colonic motility. Giant migrating contractions (GMCs) of the colon were invariably detected during defecation and tended to increase during the dark period, thereby indicating that colonic motility has a circadian rhythm. Given that GMCs in the suncus were observed immediately after feeding during the dark period, we assume the occurrence of a gastrocolic reflex in suncus, similar to that observed in humans and dogs. We also examined the factors that regulate suncus GMCs. Intravenous administration of 5‐HT (100 µg/kg), substance P (10 and 100 µg/kg), calcitonin gene‐related peptide (10 µg/kg), and α2 adrenergic receptor antagonist yohimbine (0.5, 1, and 3 mg/kg) induced GMC‐like contractions, as did intragastric and intracolonic administration of the transient receptor potential vanilloid 1 agonist, capsaicin (1 mg/kg). Conclusions & Inferences: These results indicate that the fundamental mechanisms of colonic motility in suncus are similar to those in humans and dogs, and we thus propose that suncus could serve as a novel small animal model for studying colonic motility. [ABSTRACT FROM AUTHOR]

Under severe calorie restriction (CR), the ghrelin‐growth hormone axis in mice is involved in the maintenance of plasma glucose levels. Ghrelin, a stomach‐derived acylated peptide, is up‐regulated by the sympathetic nerve in the negative energy status. Central corticotrophin‐releasing factor receptor (CRF‐R) signalling stimulates the sympathetic tone. The present study aimed to examine the effect of central CRF‐R signalling on the maintenance of plasma glucose concentrations in severe calorie‐restricted mice with the involvement of ghrelin. Intracerebroventricular injections of urocorin‐1 and urocorin‐2, which are natural ligands for CRF‐R1 and CRF‐R2, elevated plasma ghrelin concentrations and ghrelin elevation with an i.c.v. injection of urocorin‐1 was cancelled by atenolol (β1 adrenergic receptor antagonist) administration. We then established a mice model of 60% CR and found that the administration of [d‐Lys3]‐GHRP‐6 (a ghrelin receptor antagonist) in mice under 60% CR reduced the plasma glucose concentration more compared to the vehicle mice. Similarly, the atenolol injection in mice under 60% CR significantly reduced the plasma glucose concentration, which was rescued by the co‐administration of ghrelin. An i.c.v. injection of the alpha helical CRH, a non‐selective corticotrophin‐releasing factor receptor antagonist, in mice under 60% CR significantly reduced the plasma glucose concentration, although the co‐administration of α‐helical CRH with ghrelin maintained plasma glucose levels. These results suggest that central CRF‐R signalling is involved in the maintenance of plasma glucose levels in mice under severe CR via the sympathetic‐ghrelin pathway. [ABSTRACT FROM AUTHOR]

Motilin, a 22‐amino‐acid peptide produced in the upper small intestine, induces strong gastric contraction in fasted state. In many rodents, motilin and its cognate receptors exist as pseudogenes, which has delayed motilin research in the past decades. Recently, the house musk shrew (Suncus murinus) was developed as a useful model for studying motilin and gastrointestinal motility. However, due to a lack of motilin‐producing cell lines and difficulties in culturing small intestinal cells, the regulatory mechanisms of motilin secretion and its messenger RNA (mRNA) transcription have remained largely unclear. In this study, we generated small intestinal organoids from S. murinus for the first time. Using methods similar to mouse organoid generation, we found crypt‐like budding structures 3 days after isolating intestinal tissues. The organoids grew gradually with time. In addition, the generated organoids were able to be passaged and maintained for 6 months or longer. Motilin messenger RNA (mRNA) and immunopositive cells were observed in both S. murinus intestinal organoids and primary tissues. This is the first report of intestinal organoids in S. murinus, and our results suggest that S. murinus intestinal organoids could be useful for analyzing motilin secretion and transcription. [ABSTRACT FROM AUTHOR]

Ghrelin is abundantly produced in the stomach. Here, we found that glutamate decreased ghrelin expression and release in ghrelin-producing cells, and decreased levels of food intake and plasma acyl-ghrelin in mice. Treatment with siRNA of G protein-coupled receptor, family C, group 5, member B (GPRC5B) in ghrelin-producing cell lines completely blocked the effect of glutamate-induced ghrelin suppression. In addition, glutamate inhibited ghrelin release via the extracellular signalregulated kinase (ERK) activity pathway, and stimulated CREB2 mRNA expression in ghrelin-producing cell lines. These results suggest that glutamate inhibits ghrelin release via ERK-CREB2 pathway. These results suggest that the GPRC5B-ERKCREB2 pathway is involved in the inhibition of ghrelin expression and secretion in ghrelin cells. [ABSTRACT FROM AUTHOR]

The hormones leptin and ghrelin act in apposition to one another in the regulation of body weight homeostasis. Interestingly, both leptin receptor expression and ghrelin receptor expression have been observed within many of the same nuclei of the central nervous system (CNS), suggesting that these hormones may act on a common population of neurons to produce changes in food intake and energy expenditure. In the present study we explored the extent of this putative direct leptin and ghrelin interaction in the CNS and addressed the question of whether a loss of ghrelin signaling would affect sensitivity to leptin. Using histological mapping of leptin receptor and ghrelin receptor expression, we found that cells containing both leptin receptors and ghrelin receptors are mainly located in the medial part of the hypothalamic arcuate nucleus. In contrast, coexpression was much less extensive elsewhere in the brain. To assess the functional consequences of this observed receptor distribution, we explored the effect of ghrelin receptor deletion on leptin sensitivity. In particular, the responses of ad libitum-fed, diet-induced obese and fasted mice to the anorectic actions of leptin were examined. Surprisingly, we found that deletion of the ghrelin receptor did not affect the sensitivity to exogenously administrated leptin. Thus, we conclude that ghrelin and leptin act largely on distinct neuronal populations and that ghrelin receptor deficiency does not affect sensitivity to the anorexigenic and body weight-lowering actions of leptin. J. Comp. Neurol. 520:281-294, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In this article, we build models to predict the existence of citations among papers by formulating link prediction for 5 large-scale datasets of citation networks. The supervised machine-learning model is applied with 11 features. As a result, our learner performs very well, with the F1 values of between 0.74 and 0.82. Three features in particular, link-based Jaccard coefficient difference in betweenness centrality, and cosine similarity of term frequency-inverse document frequency vectors, largely affect the predictions of citations. The results also indicate that different models are required for different types of research areas-research fields with a single issue or research fields with multiple issues. In the case of research fields with multiple issues, there are barriers among research fields because our results indicate that papers tend to be cited in each research field locally. Therefore, one must consider the typology of targeted research areas when building models for link prediction in citation networks. [ABSTRACT FROM AUTHOR]

Nav1.8 is a tetrodotoxin-resistant sodium channel present in large subsets of peripheral sensory neurons, including both spinal and vagal afferents. In spinal afferents, Nav1.8 plays a key role in signaling different types of pain. Little is known, however, about the exact identity and role of Nav1.8-expressing vagal neurons. Here we generated mice with restricted expression of tdTomato fluorescent protein in all Nav1.8-expressing afferent neurons. As a result, intense fluorescence was visible in the cell bodies, central relays, and sensory endings of these neurons, revealing the full extent of their innervation sites in thoracic and abdominal viscera. For instance, vagal and spinal Nav1.8-expressing endings were seen clearly within the gastrointestinal mucosa and myenteric plexus, respectively. In the gastrointestinal muscle wall, labeled endings included a small subset of vagal tension receptors but not any stretch receptors. We also examined the detailed innervation of key metabolic tissues such as liver and pancreas and evaluated the anatomical relationship of Nav1.8-expressing vagal afferents with select enteroendocrine cells (i.e., ghrelin, glucagon, GLP-1). Specifically, our data revealed the presence of Nav1.8-expressing vagal afferents in several metabolic tissues and varying degrees of proximity between Nav1.8-expressing mucosal afferents and enteroendocrine cells, including apparent neuroendocrine apposition. In summary, this study demonstrates the power and versatility of the Cre-LoxP technology to trace identified visceral afferents, and our data suggest a previously unrecognized role for Nav1.8-expressing vagal neurons in gastrointestinal functions. J. Comp. Neurol. 519:3085-3101, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

As academic disciplines are segmented and specialized, it becomes more difficult to capture relevant research areas precisely by common retrieval strategies using either keywords or journal categories. This paper proposes a method of measuring the relatedness among sets of academic papers in order to detect unrelated communities which are not related to target topic. A citation network, extracted by given keywords, is divided into communities based on the density of links. We measured and compared four measures of relatedness between two communities in a citation network for three large-scale citation datasets. We used both link and semantic similarities. The topological distance from the center in a citation network is a more efficient measure for removing the unrelated communities than the other three measures: the ratio of the number of intercluster links over the all links, the ratio of the number of common terms over all terms, cosine similarity of tf-idf vectors. [ABSTRACT FROM AUTHOR]